Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study
Authors: June Fabian, Robert Kalyesubula, Joseph Mkandawire, Christian Holm Hansen, Dorothea Nitsch, Eustasius Musenge, Wisdom P Nakanga, Josephine E Prynn, Gavin Dreyer, Tracy Snyman, Billy Ssebunnya, Michele Ramsay, Liam Smeeth, Stephen Tollman, Saraladevi Naicker, Amelia Crampin, Robert Newton, Jaya A George, Laurie Tomlinson, Louis Banda, Steven Bello, Keith Branson, Christina Chisambo, Odala Chithodwe, Charity Kanyenda, Cynthia Katundu, Noel Kayange, Marriot Kayolo, Veronica Kuchipanga, Dorothy Makoka Kyumba, Adrian Malunga, Beatson Mvula, Elisah Mweso, Efrida Mwiba, Lydia Ngwira, Lawrence Nkhwazi, Maureen Thindwa, Itayi Adams, Kelly Barrow, Claudia Beltramo, Carolyn Bouter, Geoffrey Candy, Shingirai Chipungu, Tafadzwa Chitagu, Phumzile Dlamini, Xavier Gomez Olive Casas, Mwawi Gondwe, Pearl Gumede, Chodziwadziwa Kabudula, Brenda Kagodora, Kathleen Kahn, Lungile Khambule, Bongekile Khoza, Dorcus Khoza, Simon Khoza, Weekend Khoza, Jonathan Levin, Dorcas Lesolang, Melody Mabuza, Heather Maher, Nontsikeleko Mahime, Willy Malupi, Gontse Maphatahanyi, Nonhlanhla Mashaba, Gift Mathebula, Busisiwe Mayindi, Brian Mdaka, Memory Mhembere, Mevian Mkansi, Rrhandzu Mnisi, Vusi Mnisi, Conrad Mogane, Tshepiso Mokoena, Walter Ndlovu, Zandy Ndlovu, Fortunate Ngobeni, Khanyisile Ngobeni, Nyiko Ngobeni, Tsakani Ngobeni, Ngoni Ngwarai, Doreen Nkuna, Median Ntimane, Terrence Ntimane, Obed Nxumalo, Daniel Ohene-Kwofie, Florah Sihlangu, Bianca Silubane, Cassandra Soo, Jeffrey Tibane, Rhian Twine, Surprise Ubisi, Mboyo-Di-Tamba Vangu, Alisha Nicole Wade, Floidy Wafawanaka, Gershim Asiki, Dominic Bukenya, Innocent Erone, Grace Tumwekase, Elizabeth Kabunga, Ayoub Kakande, Pontiano Kaleebu, Anatoli Kamali, Ronald Asuptas Kiranda, Sylivia Kushemererwa, Moses Kwizera, Kagina Josephine Nabukenya, Teddy Nakimera, Cptilda Naluggwa, Sureyah Nassimbwa, Moffat Nyirenda, Rose Nabwato, Ronald Makanga, Janet Seeley, Nambi Eva Sejjemba, Grace Seremba, Vincent Alumadri, Nick Bird
Journal: The Lancet Global Health (2022)

BackgroundThe burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations.MethodsWe measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa.FindingsOf 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m2 either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa.InterpretationEstimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed.FundingThe GSK Africa Non-Communicable Disease Open Lab.TranslationsFor the Luganda, Chichewa and Xitsonga translations of the abstract see Supplementary Materials section.